TY - JOUR
T1 - Water-soluble lipopolymer delivery of N-methyl-D-aspartic acid receptor 2B siRNA relieves chronic neuropathic pain in rats
AU - Lu, Jianhua
AU - Tao, Yuanxiang
AU - Yang, Xue
AU - Tu, Weifeng
AU - Chen, Hao
AU - Xiong, Jiaxiang
AU - Hu, Chungui
PY - 2011
Y1 - 2011
N2 - Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B (NR2B) overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA (siRNA) can inhibit NR2B expression, siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury. However, an efficient and safe vector for NR2B siRNA has not been discov- ered. This study shows that a water soluble lipopolymer (WSLP) comprised of low molecular weight polyethyleneimine (PEI) and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP/siRNA complexes for 3 days in- hibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respec- tively, compared with control rats (P < 0.01). Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3, 7, 12, and 21 days, while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.
AB - Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B (NR2B) overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA (siRNA) can inhibit NR2B expression, siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury. However, an efficient and safe vector for NR2B siRNA has not been discov- ered. This study shows that a water soluble lipopolymer (WSLP) comprised of low molecular weight polyethyleneimine (PEI) and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP/siRNA complexes for 3 days in- hibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respec- tively, compared with control rats (P < 0.01). Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3, 7, 12, and 21 days, while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.
KW - N-Methyl-D-aspartic acid receptor 2B
KW - Neuropathic pain
KW - Peripheral nerve injury
KW - Small interfering RNA
KW - Water soluble lipopolymer
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U2 - 10.3969/j.issn.1673-5374.2011.29.007
DO - 10.3969/j.issn.1673-5374.2011.29.007
M3 - Article
AN - SCOPUS:81755176508
SN - 1673-5374
VL - 6
SP - 2279
EP - 2283
JO - Neural Regeneration Research
JF - Neural Regeneration Research
IS - 29
ER -